Gene expression profiling analysis reveals weaning-induced cell cycle arrest and apoptosis in the small intestine of pigs1

Abstract

In swine production, weaning is a critical event for porcine weaning-associated disease, such as postweaning stress syndrome, which involves intestinal dysfunction. However, little is known about the molecular mechanisms of intestinal dysfunction in pigs during weaning. To gain new insight into the interaction between weaning stress and intestinal function, 4 pigs at 25 d of age for each of the weaning and the suckling groups for a total of 40 pigs were used to analyze changes in the genomic expression in the intestines of weaned pigs by microarray analysis. Four hundred forty-five genes showed altered expression after weaning treatment (286 upregulated and 159 downregulated) at the cutoff criteria of the fold change ≥1.5 or <0.67 and P < 0.05. Most of these altered genes are cellular process related and regulators that may be involved in biological regulation, developmental processes, and metabolic processes. A keen interest was paid in deciphering expression changes in apoptosis or cell cycle control genes. The altered genomic expression of 8 selected genes related to the cell cycle process was confirmed by quantitative real-time PCR. Of the 8 genes tested, increased (P < 0.05) expression of genes involved in apoptosis (cytochrome c, somatic, and ataxia telangiectasia mutated), pro-inflammatory signals (tumor necrosis factor and NO synthases 2), and a transcription factor (nuclear factor of activated T cells, cytoplasmic, and calcineurin-dependent 2) were detected in weaned pigs compared with suckling pigs, but the expression of cell cycle control-related genes, such as E2F transcription factor 5-like, was lower (P < 0.05) in weaned pigs than suckling pigs. Weaned pigs also showed increased interleukin 8 expression and decreased SMAD family member 4 expression although no significant differences (P > 0.05) were observed when compared with the suckling pigs. These selected genes likely indicate that weaning induced cell cycle arrest, enhanced apoptosis, and inhibited cell proliferation. The results of this study provide a basis for understanding the molecular pathogenesis of weaning treatment.